Chromatin remodeling protein HELLS is critical for retinoblastoma tumor initiation and progression.

Retinoblastoma is an aggressive childhood cancer of the developing retina that initiates by biallelic RB1 gene inactivation. Tumor progression in retinoblastoma is driven by epigenetics, as retinoblastoma genomes are stable, but the mechanism(s) that drive these epigenetic changes remain unknown. Lymphoid-specific helicase (HELLS) protein is an epigenetic modifier directly regulated by the RB/E2F pathway. In this study, we used novel genetically engineered mouse models to investigate the role of HELLS during retinal development and tumorigenesis. Our results indicate that Hells-null retinal progenitor cells divide, undergo cell-fate specification, and give rise to fully laminated retinae with minor bipolar cells defects, but normal retinal function. Despite the apparent nonessential role of HELLS in retinal development, failure to transcriptionally repress Hells during retinal terminal differentiation due to retinoblastoma (RB) family loss significantly contributes to retinal tumorigenesis. Loss of HELLS drastically reduced ectopic division of differentiating cells in Rb1/p107-null retinae, significantly decreased the incidence of retinoblastoma, delayed tumor progression, and increased overall survival. Despite its role in heterochromatin formation, we found no evidence that Hells loss directly affected chromatin accessibility in the retina but functioned as transcriptional co-activator of E2F3, decreasing expression of cell cycle genes. We propose that HELLS is a critical downstream mediator of E2F-dependent ectopic proliferation in RB-null retinae. Together with the nontoxic effect of HELLS loss in the developing retina, our results suggest that HELLS and its downstream pathways could serve as potential therapeutic targets for retinoblastoma

Tectonic and climatic controls on the Chuquibamba landslide (western Andes, southern Peru)

The contribution of landslides to the Quaternary evolution of relief is poorly documented in arid contexts. In southern Peru and northern Chile, several massive landslides disrupt the arid western Andean front. The Chuquibamba landslide, located in southern Peru, belongs to this set of large landslides. In this area, the Incapuquio fault system captures the intermittent drainage network and localizes rotational landslides. Seismic activity is significant in this region with recurrent Mw9 subduction earthquakes; however, none of the latest seismic events have triggered a major landslide. New terrestrial cosmogenic dating of the Chuquibamba landslide provides evidence that the last major gravitational mobilization of these rotational landslide deposits occurred at ~ 102 ka, during the Ouki wet climatic event identified on the Altiplano between 120 and 98 ka. Our results suggest that wet events in the arid and fractured context of the Andean forearc induced these giant debris flows. Finally, our study highlights the role of tectonics and climate on (i) the localization of large Andean landslides in the Western Cordillera and on (ii) the long-term mass transfer to the trench along the arid Andean front

Observations and dynamical implications of active normal faulting in South Peru

SUMMARY Orogenic plateaus can exist in a delicate balance in which the buoyancy forces due to gravity acting on the high topography and thick crust of the plateau interior are balanced by the compressional forces acting across their forelands. Any shortening or extension within a plateau can indicate a perturbation to this force balance. In this study, we present new observations of the kinematics, morphology and slip rates of active normal faults in the South Peruvian Altiplano obtained from field studies, high-resolution DEMs, Quaternary dating and remote sensing. We then investigate the implications of this faulting for the forces acting on the Andes. We find that the mountains are extending ∼NNE–SSW to ∼NE–SW along a normal fault system that cuts obliquely across the Altiplano plateau, which in many places reactivates Miocene-age reverse faults. Radiocarbon dating of offset late Quaternary moraines and alluvial fan surfaces indicates horizontal extension rates across the fault system of between 1 and 4 mm yr–1—equivalent to an extensional strain rate in the range of 0.5–2 × 10−8 1 yr–1 averaged across the plateau. We suggest the rate and pattern of extension implies there has been a change in the forces exerted between the foreland and the Andes mountains. A reduction in the average shear stresses on the sub-Andean foreland detachment of ≲4 MPa (20–25 per cent of the total force) can account for the rate of extension. These results show that, within a mountain belt, the pattern of faulting is sensitive to small spatial and temporal variations in the strength of faults along their margins.Denman Baynes Senior Studentship, Clare College Cambridge Arup Santander Mobility Grant (University of Cambridge

Selection indices to identify drought-tolerant grain sorghum cultivars.

Twenty-five cultivars of grain sorghum [Sorghum bicolor (L.) Moench] were examined under both drought stress and normal conditions in 4 experiments. In each condition, genotypes were evaluated in a factorial experiment using a randomized complete block design with 3 replications. Eight drought tolerance indices including stability tolerance index, mean productivity (MP), geometric MP, harmonic mean, stress susceptibility index, tolerance index, yield index, and yield stability index were estimated for each genotype based on grain yield under drought (Ys) and irrigated conditions (Yp). The results indicated that there were positive and significant correlations among Yp and Ys with geometric MP, MP, harmonic mean, and stability tolerance index, indicating that these factors are better predictors of Yp and Ys than tolerance index, stress susceptibility index, yield stability index, and yield index. Based on adjusted means at Yp and Ys, indices geometric MP, MP, harmonic mean, and stability tolerance index, unweighted pair group method with arithmetic mean cluster and biplot analysis, the most tolerant cultivars were ?9929020?, ?9929034?, and ?N 95B?

Training Materials Utilizing Food Choices for Healthful Living

As the instructor for this program you have the unique opportunity to help communities achieve a healthier lifestyle, enjoy the benefits of good nutrition and be successful at managing Diabetes.This three part series contains practical information that is designed to be educational and interactive. The goal of this curriculum is to bring up-to-date nutrition and Diabetes information to individuals that provide nutrition and health education. We welcome your enthusiasm and sensitivity and hope you find the information useful.Funding by the United States Department of Agriculture, Cooperative State Research, Education, and Extension Service Grant Number: 94- 38826-0179

Evaluación de la calidad de comunicación entre niveles asistenciales mediante el documento interconsulta

ObjetivosEvaluar la calidad y mejora de cumplimentación de los documentos de interconsulta en el equipo de atención primaria (EAP).DiseñoCiclo completo de calidad.EmplazamientoAtención primaria (AP).Componentes de la evaluaciónDimensión estudiada: calidad científico-técnica. Sujetos: todos los documentos de interconsulta (DI-1) dirigidos por los médicos de AP del centro de salud de Irún Centro a atención especializada durante 15 días, 223 DI-1 para la evaluación en abril de 1998 y 287 para la reevaluación en octubre 1998. Tipo de evaluación: retrospectiva. Fuente de datos: documentos interconsulta e historias clínicas. Criterios: explícitos y normativos. Medidas correctoras: educativas (discusión de resultados en reunión del EAP).ResultadosEn la reevaluación se observó una mejoría estadísticamente significativa: datos de filiación (91,5-96,8%), legibilidad (86-92,7%), antecedentes y/o medicación habitual (35,9-50%) y sintomatología (77,8-87,2%). Por niveles de calidad se ha pasado en los buenos del 20,6 al 42,5% y en los malos del 40,8 al 33,4%. Obtuvimos respuesta en un 22,2% de nuestras derivaciones. La falta de respuesta se produce en un 34% por no haber informe del especialista, un 47,8% se atribuyen al paciente o al circuito y el 18% de los pacientes está pendiente de pruebas.ConclusionesLa información proporcionada en los DI-1 ha mejorado significativamente después del ciclo de calidad. Conocer nuestra práctica habitual de trabajo sirve como estimulo de mejora. Los criterios que peor cumplimos son: referencia a antecedentes personales y/o medicación habitual, exploración física y medidas terapéuticas empleadas. Gran perdida de información en la respuesta a nuestras derivaciones.ObjectivesTo evaluate the quality and improvement of compliance in the inter-consultation documents of the primary care team (PCT).DesignEntire care cycle.SettingPrimary care (PC).MeasurementsDimension studied: scientific-technical quality. Subjects: all the inter-consultation documents (ID-1) sent by PC doctors from Irun Health Centre to specialist clinics over a 15-day period. 223 ID-1 for evaluation in April 1998, and 287 for re-evaluation in October 1998. Type of evaluation: retrospective. Source of data: inter-consultation documents and clinical records. Criteria: explicit and standard. Corrective measures: educational (discussion of results in meeting of the PCT).ResultsA statistically significant improvement was found at the re-evaluation: basic personal details (91.5%-96.8%), legibility (86%-92.7%), medical history and/or customary medication (35.9%-50%) and symptoms (77.8%-87.2%). Good quality levels rose from 20.6% to 42.5%; and bad quality levels fell from 40.8% to 33.4%. 22.2% of our referrals received a reply. 34% of the lack of replies was because of no report from the specialist, 47.8% were attributed to the patient or circuit, and 18% of the patients were awaiting test results.ConclusionsThe information supplied in the ID-1 improved significantly after the quality cycle. Knowing our habitual working practice can serve to stimulate improvement. The criteria we complied with least were: reference to personal antecedents and/or habitual medication, physical examination, and therapeutic measures employed. There was a huge loss of information in the replies to our referrals

Social Support and Substance Use as Moderators of the Relationship Between Depressive Symptoms and Suicidal Ideation in Adolescents

Indexación: Scopus.Literature reports that depressive symptoms may precede suicidal ideation. Several studies have identified social support and substance use as moderators of this relationship. However, no study has evaluated these variables together by testing how substance use can affect the moderating effect of social support in this relationship. The purpose of this article is to individually evaluate dimensions of social support (friends, family, significant others, and school) and substance use (alcohol, marijuana, and other illicit drugs), as moderators of the relationship between depressive symptoms and suicidal ideation, as well as analyze the moderating role of substance use in the moderation exerted by social support in this relationship. This study, quantitative and cross-sectional, considered 775 adolescents [Average age = 15.48 (SD = 0.96), 45.9% women], from 20 randomly selected schools in Santiago de Chile. Simple moderation models were used to analyze possible moderators separately, and double moderation models were used to analyze the moderating role of substance use in the moderating effect of social support. The results show that the four dimensions of social support moderate the relationship between depressive symptomatology and suicidal ideation, showing the strongest interaction in the case of family support, followed by support of a significant person, support at school, and support of friends, in that order. On the other hand, alcohol was the only drug that moderated the relationship in question. In addition, the results show that the use of alcohol limits the moderating effect of social support in the fields of family, significant person, and school support, but not in the case of support of friends. The use of marijuana and other illicit drugs did not affect the moderating effects of social support for any of the areas evaluated. The results are discussed according to the different roles that alcohol use can play in adolescence, and how these, together with perceived social support, are related to the emergence of suicidal ideation from depressive symptoms. © Copyright © 2020 Rubio, Oyanedel, Cancino, Benavente, Céspedes, Zisis and Páez.https://www.frontiersin.org/articles/10.3389/fpsyg.2020.539165/ful

Spanish children's diet: compliance with nutrient and food intake guidelines

OBJECTIVE: To compare the diet of Spanish children against the nutrient and food intake guidelines. To calculate an index of overall diet quality and check its validity against nutrient intake. DESIGN AND SETTING: Cross-sectional study in four cities in Spain, where information on food and nutrient intake was obtained from schoolchildren through a food frequency questionnaire. PARTICIPANTS: The sample included 1112 children (overall response rate of 85%) attending public and private schools and aged 6-7 y. Children were selected through random cluster sampling in schools, and stratified by sex and socioeconomic level. MAIN OUTCOME MEASURES: Mean nutrient intake, number of food servings, and the percentage of children who meet recommended nutrient and food-serving intake levels. The overall dietary quality was assessed using the Healthy Eating Index (HEI). RESULTS: Mean micronutrient intake exceeded 100% of the recommended dietary allowances, except for vitamin B6, which registered a mean intake of 77.1%. For almost all children, intake of saturated fat was above, and that of carbohydrate below, the recommended level, in contrast to the relatively high compliance with the recommendations for poly- and monounsaturated fatty acid, salt and fiber intake (69.7, 43.7, 40.7, and 30.1%, respectively). Consumption of food servings for each of the five American pyramid food groups came close to or exceeded USDA guidelines, with the exception of cereals, with 5.4 servings per day. The mean score obtained in the HEI was 64.6. Children who complied with all the food guide pyramid recommendations registered a higher dietary variety and a healthier nutritional profile. CONCLUSIONS: Children aged 6-7 y show scant compliance with the macronutrient goals for healthy eating. Micronutrient intake is adequate in general, yet there are small groups of children with risk of deficient intake of vitamins B6 and D. While Spanish children's eating habits are reasonably in line with American food guide pyramid guidelines, consumptions of cereals and fruit should be improved.This study was partly funded by grants from the Inter-national Olive Oil Board (Consejo Oleı ́cola Internacional),Comunidad de Madrid, Fundacio ́n Pedro Barrie ́de laMaza, and Fundacio ́n Eugenio Rodrı ́guez Pascua